Controlled release (CR) formulations are useful in situations where drug release over an extended period of time is required, such as repetitive, intermittent dosings of a drug from one or more immediate release systems. Controlled release drug delivery systems are used to improve the therapeutic response by providing blood levels that are more consistent and stable compared to immediate release dosage forms. Existing CR dosage forms are typically based on matrix tablets or coated tablets or capsules filled with coated drug particles or granules. These systems have several drawbacks, however including the lack of content uniformity and homogeneity, particularly with compounds present in low dosages. Moreover, compounds which are used in low dosages, as well as compounds which are moisture sensitive, can be difficult to handle in solid form, which is the form typically used to prepare tablets or powder-filled hard gelatin capsules.
U.S. Patent Application Publication No. 2004/0052731 to Hirsh et al. describes abuse deterrent pharmaceutical compositions. The compositions contain a drug which has been modified to increase its lipophilicity. The modified drug is dispersed within microparticles composed of a material that is either slowly soluble or not soluble in water. The drug containing microparticles or drug particles can be coated with one or more coating layers, where at least one coating is water insoluble and preferably organic solvent insoluble, but enzymatically degradable by enzymes in the GI tract.
Controlled release formulations, particularly of drugs which are prone to abuse such as opioid analgesics, can be susceptible to misuse. Currently available sustained release formulations of such drugs, which contain a relatively large amount of drug meant to be released from the formulation over an extended period of time, are particularly attractive to abusers since the sustained release action can be destroyed by crushing or grinding the formulation. The resulting material (i.e., the crushed formulation) can no longer control the release of drug. Depending on the drug, abusers can then snort the material, swallow the material or dissolve the material in water and subsequently inject it intravenously. The dose of drug contained in the formulation is thus absorbed immediately through the nasal or GI mucosa (for snorting or swallowing, respectively) or is administered in a bolus to the systemic circulation (for IV injection). These methods result in the rapid bioavailability of relatively high doses of drug, giving the abuser a “high”. Since relatively simple methods (crushing, grinding, chewing and/or dissolution in water) can be used to transform such formulations into an abusable form, they provide virtually no deterrent to a potential abuser.
There is a need for a liquid controlled-release composition in which low dose compounds and compounds which are moisture sensitive can be more easily formulated.
There also exists a need for a controlled release formulation which can minimize or prevent the misuse of drugs which are prone to abuse by making it more difficult for the drug to be extracted from the dosage form.
Therefore, it is an object of the present invention to provide a dual controlled release matrix for the formulation of low dose and/or moisture sensitive drugs, and methods of manufacture thereof.
It is further an object of the invention to provide a dual controlled release matrix which can minimize or prevent the misuse of drugs which are prone to abuse.